The broad aim of the project is to determine the effects of ethanol and its metabolites on the metabolic and electrical activeities of the brain. The experimental study will use an isolated, perfused rat brain preparation which will avoid indirect effects from the rapid metabolism of ethanol by liver and which will permit easy control of experimental conditions which is not possible in the intact animal. In our isolated brain preparation the blood-brain barrier is intact and the tissue ultrastructure (electron micrograph) is indistinguishable from that of the brain of the normal rat. The effects of ethanol and acetaldehyde on the brain will be examined in three ways: (1) biochemically to determine the energy status, the oxidation-reduction status and the levels of substrates and intermediary metabolites in the brain tissue; (2) histochemically and chemically to measure changes in the biogenic amines in the brain; (3) electrophysiologically to measure the influences on the spontaneous and evoked electrical activity in discrete areas of the brain, and to measure the effects of ethanol and acetaldehyde on the changes caused by electrical stimulation of discrete areas. Ethanol and/or acetaldehyde will be added to the perfusion fluid or administered, in acute or chronic dosage, to the rat from which the isolated brain preparation is subsequently made. The perfusion fluid will be examined for ethanol and glucose utilization, concentrations of lactate and pyruvate, metabolites (acetaldehyde, acetoin, etc.) and for amines, amino acids, and metabolites which may be released from the brain by the action of ethanol or acetaldehyde or by electrical stimulation.